All tumors are characterized by both inappropriate growth and anaplasia, the loss of differentiated characteristics. Research in Dr Israel's laboratory concerns the molecular pathways over which these two key biologic activities, growth and differentiation, are coordinately regulated. Investigations are also ongoing on the role of aberrations in these pathways in the development of cancer. Recent work has been focused on the characterization and evaluation of Id genes. These genes encode transcription factors that function as dominant negative inhibitors of basic helix-loop-helix proteins, which mediate lineage-specific gene expression. Id genes are ubiquitously expressed throughout early development, though they are rarely expressed in tissues from adults. Work in this laboratory has shown that these genes are also highly expressed in many different types of brain tumors. Expression of Id-2 can enhance cell growth, and our work has determined that this is mediated through a direct interaction with the product of the retinoblastoma gene, a known tumor suppressor. Ongoing work is focused on further characterization of the cellular pathways that mediate Id-gene induced cell growth and especially the role of microRNAs in this process are underway. Experiments have been conducted to understand the precise cell types especially the stem cell variants in which tumors of the CNS arise, and the molecular alterations that characterize histologically indistinguishable tumors of astrocytes are being studied. These studies have involved the identification of novel tumor markers, as well as the characterization of known tumor cell markers in various types of CNS tumors. Of particular interest has been the
examination of genes whose expression is regulated during the course of nervous system differentiation and oncogenes and tumor suppressor genes whose structure and expression is altered in brain tumors.